MTA family of proteins in DNA damage response: mechanistic insights and potential applications.
MTA family of proteins in DNA damage response: mechanistic insights and potential applications.
复制标题
DNA 损伤反应中的 MTA 蛋白家族：机制见解和潜在应用
DOI：
10.1007/s10555-014-9524-2
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发表时间：
2014-12
影响因子：
9.2
通讯作者：
Kumar, Rakesh
中科院分区：
文献类型：
--
作者：
Li, Da-Qiang;Yang, Yinlong;Kumar, Rakesh
关键词：
DNA损伤，尤其是DNA双链断裂，严重威胁着哺乳动物基因组的稳定性。基因组完整性的维持在很大程度上依赖于染色质背景下有效、准确和及时的DNA损伤反应。因此，DNA损伤反应机制的失调从根本上与基因组不稳定性和可能的癌症易感性有关。反过来，人类癌症中DNA损伤反应途径的异常激活使肿瘤细胞能够在DNA损伤中存活，从而导致肿瘤细胞对DNA损伤性放射疗法和化学疗法产生抗性。大量的实验证据表明，ATP依赖的染色质重塑和组蛋白修饰在DNA损伤反应中起着重要作用。作为核小体重塑和组蛋白去乙酰化酶（NuRD）复合物的一个组成部分，该复合物耦合ATP依赖的染色质重塑和组蛋白去乙酰化酶活性，转移相关蛋白（MTA）家族蛋白最近已被证明参与DNA损伤反应，超出其在基因转录中的公认作用。在这篇专题综述中，我们将重点介绍我们目前对MTA家族蛋白在DNA损伤反应中的作用及其在DNA损伤抗癌治疗中的潜在意义的理解。
The DNA damage, most notably DNA double-strand breaks, poses a serious threat to the stability of mammalian genome. Maintenance of genomic integrity is largely dependent on an efficient, accurate, and timely DNA damage response in the context of chromatin. Consequently, dysregulation of the DNA damage response machinery is fundamentally linked to the genomic instability and a likely predisposition to cancer. In turn, aberrant activation of DNA damage response pathways in human cancers enables tumor cells to survive DNA damages, thus, leading to the development of resistance of tumor cells to DNA damaging radio- and chemotherapies. A substantial body of experimental evidence has established that ATP-dependent chromatin remodeling and histone modifications play a central role in the DNA damage response. As a component of the nucleosome remodeling and histone deacetylase (NuRD) complex that couples both ATP-dependent chromatin remodeling and histone deacetylase activities, the metastasis-associated protein (MTA) family proteins have been recently shown to participate in the DNA damage response beyond its well-established roles in gene transcription. In this thematic review, we will focus on our current understandings of the role of the MTA family proteins in the DNA damage response and their potential implications in DNA damaging anticancer therapy.
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影响因子：
10.5
作者：
Guo, ZJ;Kumagai, A;Dunphy, WG
通讯作者：
Dunphy, WG
影响因子：
64.5
作者：
Bao, Yunhe;Shen, Xuetong
通讯作者：
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影响因子：
5.3
作者：
Ding, ZH;Gillespie, LL;Paterno, GD
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影响因子：
50.3
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通讯作者：
Hiebert SW
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ